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Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas.

Abstract : OBJECTIVE: Previous work from our laboratory has demonstrated that frog urotensin-II (UII), at a high concentration, inhibits glucose-induced insulin release in the rat pancreas. We have investigated the effect of rat UII and two structural analogs on insulin secretion and searched for the presence of UII-immunoreactivity in rat pancreatic extracts. METHODS: The study was performed in the perfused rat pancreas. UII as well as its analogs were synthesized by solid phase methodology. Pancreatic extracts were analyzed for UII by reversed-phase HPLC combined with a sensitive UII RIA. RESULTS: Infusion of synthetic rat UII inhibited glucose-induced insulin release in a dose-dependent manner (IC(50): 0.12 nmol/l). UII (1 nmol/l) also inhibited the insulin responses induced by carbachol, glucagon-like peptide-1, and a calcium channel agonist (BAY K 8644). The inhibitory effect of UII was mimicked by the potent G protein-coupled receptor (GPR14) agonist [3-iodo-Tyr(6)]UII(4-11). In contrast, [Ala(8)]UII(4-11), a UII analog devoid of contractile activity on rat aortic rings, did not affect glucose-induced insulin secretion. Analysis of rat pancreatic extracts revealed the presence of an immunoreactive peptide exhibiting the same retention time as synthetic rat UII. CONCLUSIONS: Our results demonstrate that UII is a potent insulinostatic peptide. The observation that UII is actually present in the pancreas suggests that this peptide may play a physiological role in the control of insulin secretion. Concerning the two UII analogs tested, only [3-iodo-Tyr(6)]UII(4-11), reportedly possessing GPR14-mediated contractile activity, mimics the insulinostatic effect of UII. This finding would support the view that UII acts on the pancreatic beta cell through the GPR14 receptor.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-01974193
Contributor : Jérôme Leprince <>
Submitted on : Tuesday, January 8, 2019 - 4:19:06 PM
Last modification on : Monday, April 29, 2019 - 4:36:13 PM

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  • HAL Id : hal-01974193, version 1
  • PUBMED : 15588249

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Ramona Silvestre, Eva Egido, Raquel Hernández, Jérôme Leprince, David Chatenet, et al.. Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas.. European Journal of Endocrinology, BioScientifica, 2004, 151 (6), pp.803-9. ⟨hal-01974193⟩

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